Research on epigenetic regulation of aging and cancer by CHD8/histone H1 complex

我们最近发现，染色质重塑因子CHD 8通过招募染色质上的连接蛋白H1来抑制p53的功能，并预期CHD 8/组蛋白H1复合物可能在细胞衰老中的染色质重塑中起重要作用。首先，我们研究了正常细胞中CHD 8过表达对细胞衰老的影响，并揭示了CHD 8的强制表达抑制p53诱导的细胞衰老。我们接下来产生了CHD 8诱导型转基因小鼠，并揭示了CHD 8具有有效的转化活性。在正常衰老或早衰小鼠中，我们发现CHD 8/组蛋白H1的表达水平显著降低。此外，我们发现，细胞衰老诱导组蛋白H1敲除细胞或来自CHD 8敲除小鼠的细胞。综上所述，预计CHD 8不仅具有抗衰老作用，而且还具有致癌基因的功能。

We recently have found that a chromatin remodeling factor CHD8 suppresses p53 function by recruiting the linker histone H1 on chromatin, and expected that a CHD8/histone H1 complex may play an important role in chromatin remodeling in cellular senescence. First, we investigated the effect of CHD8 overexpression on cellular senescence in normal cells, and revealed that forced expression of CHD8 inhibits p53-induced cellular senescence. We next generated CHD8-inducible transgenic mice, and revealed that CHD8 has a potent transformating activity. In normal aging or premature aging mice, we found that the expression level of CHD8/histone H1 is markedly decreased. Furthermore, we found that cellular senescence is induced in histone H1-knockdown cells or the cells derived from CHD8-knockout mice. Taken together, it is expected that CHD8 not only has anti-aging effect, but also functions as an oncogene.